Biomol Ther.
2017 Jul;25(4):404-410. 10.4062/biomolther.2017.010.
A Benzylideneacetophenone Derivative Induces Apoptosis of Radiation-Resistant Human Breast Cancer Cells via Oxidative Stress
- Affiliations
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- 1School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea. jinwonh@jejunu.ac.kr
- 2Department of Neuroscience, College of Medicine, Ewha Womans University, Seoul 03760, Republic of Korea.
- 3Department of Bio and Nanochemistry, Kookmin University, Seoul 02707, Republic of Korea.
- 4Aging Research Center, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea.
- KMID: 2386907
- DOI: http://doi.org/10.4062/biomolther.2017.010
Abstract
- Benzylideneacetophenone derivative (1E)-1-(4-hydroxy-3-methoxyphenyl) hept-1-en-3-one (JC3) elicited cytotoxic effects on MDA-MB 231 human breast cancer cells-radiation resistant cells (MDA-MB 231-RR), in a dose-dependent manner, with an IC₅₀ value of 6 μM JC3. JC3-mediated apoptosis was confirmed by increase in sub-G1 cell population. JC3 disrupted the mitochondrial membrane potential, and reduced expression of anti-apoptotic B cell lymphoma-2 protein, whereas it increased expression of pro-apoptotic Bcl-2-associated X protein, leading to the cleavage of caspase-9, caspase-3 and poly (ADP-ribose) polymerase. In addition, JC3 activated mitogen-activated protein kinases, and specific inhibitors of these kinases abrogated the JC3-induced increase in apoptotic bodies. JC3 increased the level of intracellular reactive oxygen species and enhanced oxidative macromolecular damage via lipid peroxidation, protein carbonylation, and DNA strand breakage. Considering these findings, JC3 is an effective therapy against radiation-resistant human breast cancer cells.
Keyword
MeSH Terms
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Apoptosis*
bcl-2-Associated X Protein
Breast Neoplasms*
Breast*
Caspase 3
Caspase 9
Chalcone*
DNA
Extracellular Vesicles
Humans*
Lipid Peroxidation
Membrane Potential, Mitochondrial
Mitogen-Activated Protein Kinases
Oxidative Stress*
Phosphotransferases
Protein Carbonylation
Reactive Oxygen Species
Caspase 3
Caspase 9
Chalcone
DNA
Mitogen-Activated Protein Kinases
Phosphotransferases
Reactive Oxygen Species
bcl-2-Associated X Protein
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